Crohn’s Disease Successfully Treated With Infliximab in a Patient Receiving Hemodialysis: Case Report and Review of the Literature

There is limited information in the use of antitumor necrosis factor α, infliximab, in patients on hemodialysis. In Crohn’s disease (CD), only 3 cases are reported.A 76-year-old man on hemodialysis for renal failure caused by immunoglobulin A nephropathy developed diarrhea and abdominal pains. A marked edema was observed in the pretibia and ankle. An increase of C-reactive protein (CRP) and erythrocyte sedimentation rate, hypoalbuminemia, hypocholesterolemia, and moderate anemia was found. Ultrasonography and computed tomography (CT) found wall thickness in the left colon. Sigmoidoscopy revealed multiple ulcers in the sigmoid colon and noncaseating epithelioid granuloma was found in the biopsy specimen. Barium enema study exhibited collar button signs and longitudinal ulcers in the left colon.A severe form of CD was diagnosed. Metronidazole seemed to decrease CRP but was ineffective in ameliorating diarrhea. Infliximab rather than steroid hormone was chosen for the treatment. Standard induction therapy with infliximab was initiated. Symptoms rapidly improved then disappeared. CD activity index decreased from 747 to a remission level of 134 after 2 infusions of infliximab. Scheduled maintenance infliximab therapy was administered after the induction therapy. Ultrasonography and CT showed a disappearance of the wall thickness of the colon. Adverse reactions were not observed.Infliximab was effective and safe in a patient with CD on hemodialysis. Our case has added additional literature in accordance with previous reports supporting infliximab as effective and safe in patients on hemodialysis.     

Novel compound heterozygous PIGT mutations caused multiple congenital anomalies-hypotonia-seizures syndrome 3

Recessive mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor synthesis pathway have been demonstrated as causative of GPI deficiency disorders associated with intellectual disability, seizures, and diverse congenital anomalies. We performed whole exome sequencing in a patient with progressive encephalopathies and multiple dysmorphism with hypophosphatasia and identified novel compound heterozygous mutations, c.250G>T (p. Glu84*) and c.1342C>T (p. Arg488Trp), in PIGT encoding a subunit of the GPI transamidase complex. The surface expression of GPI-anchored proteins (GPI-APs) on patient granulocytes was lower than that of healthy controls. Transfection of the Arg488Trp mutant PIGT construct, but not the Glu84* mutant, into PIGT-deficient cells partially restored the expression of GPI-APs DAF and CD59. These results indicate that PIGT mutations caused neurological impairment and multiple congenital anomalies in this patient.     

Free air on CT and the risk of peritonitis in peritoneal dialysis patients: a retrospective study

Background: Intra-abdominal free air is found frequently in patients undergoing peritoneal dialysis (PD). Some studies have investigated an association between intra-abdominal free air and peritonitis in PD patients. However, most used chest X-rays, which are of limited sensitivity, and the association was not made clear. We conducted a retrospective study of the association between peritonitis and intra-abdominal free air using computed tomography. Methods: The presence and volume of free air, and its relationship with other variables, were assessed on review of routine examinations in 108 patients. Correlations between the presence of free air and age, duration of PD, continuous ambulatory versus automated PD, presence or absence of a person who assisted in bag changes, exit-site infection, tunnel infection and peritonitis were assessed. Results: Free air was detected in 29 patients (27.1%). The prevalence of peritonitis was higher in the free air (+) group than in the free air (?) group: 1/40.2 patient-months for free air (+) versus 1/96.9 patient-months for free air (?). The risk ratio of free air for peritonitis was 2.41 (95% confidence interval: 2.28–2.55) and was similar when corrected for age, gender, albumin, diabetes mellitus and body mass index. Conclusion: Free air is an independent risk factor for peritonitis in PD patients. This suggests that bag change procedures should be re-evaluated, and patients re-educated, when necessary.     

Comparison of the copy numbers of bovine leukemia virus in the lymph nodes of cattle with enzootic bovine leukosis and cattle with latent infection

To establish a diagnostic index for predicting enzootic bovine leukosis (EBL), proviral bovine leukemia virus (BLV) copies in whole blood, lymph nodes and spleen were examined by quantitative real-time PCR (qPCR). Cattle were divided into two groups, EBL and BLV-infected, based on meat inspection data. The number of BLV copies in all specimens of EBL cattle was significantly higher than those of BLV-infected cattle (p < 0.0001), and the number of BLV copies in the lymph nodes was particularly large. Over 70 % of the superficial cervical, medial iliac and jejunal lymph nodes from EBL cattle had more than 1,000 copies/10 ng DNA, whereas lymph nodes from BLV-infected cattle did not. These findings suggest that the cattle harboring more than 1,000 BLV copies may be diagnosed with EBL.     

Balloon tracheoplasty as initial treatment for neonates with symptomatic congenital tracheal stenosis

Neonates with congenital tracheal stenosis (CTS) sometimes develop respiratory distress and may be difficult to intubate. We used balloon tracheoplasty with a rigid bronchoscope for emergency airway management in neonates with symptomatic CTS. Herein, we describe the balloon tracheoplasty procedure and the early outcomes following its use as the initial treatment of neonatal symptomatic CTS. We performed a retrospective analysis of five neonates with CTS who were initially treated with balloon tracheoplasty at our institution from January 2010 to December 2013. Five patients with a mean birthweight of 2,117 g were treated during the study period. Of these, four developed respiratory distress after birth, and all patients had difficult intubations. In all five patients, definitive diagnosis of CTS was made by rigid bronchoscopy and 3-dimensional reconstruction scan. A total of nine balloon dilatations were performed in five patients. Following balloon tracheoplasty, two patients were extubated, one was extubated after resection and end-to-end anastomosis following initial balloon dilatation, and one remained hospitalized with tracheostomy for tracheomalacia. The remaining patient died from tracheal bleeding associated with congenital heart disease. Although our sample size was small, balloon tracheoplasty is a potentially effective initial treatment for selected cases with neonatal symptomatic CTS.     

Imeglimin population pharmacokinetics and dose adjustment predictions for renal impairment in Japanese and Western patients with type 2 diabetes

Imeglimin is an orally administered first‐in‐class drug to treat type 2 diabetes mellitus (T2DM) and is mainly excreted unchanged by the kidneys. The present study aimed to define the pharmacokinetic (PK) characteristics of imeglimin using population PK analysis and to determine the optimal dosing regimen for Japanese patients with T2DM and chronic kidney disease (CKD). Imeglimin plasma concentrations in Japanese and Western healthy volunteers, and patients with T2DM, including patients with mild to severe CKD with an estimated glomerular filtration rate (eGFR) greater than 14 ml/min/1.73 m² were included in a population PK analysis. PK simulations were conducted using a population PK model, and the area under concentration‐time curve (AUC) was extrapolated with power regression analysis to lower eGFR. The influence of eGFR, weight, and age on apparent clearance and of dose on relative bioavailability were quantified by population PK analysis. Simulations and extrapolation revealed that the recommended dosing regimen based on the AUC was 500 mg twice daily (b.i.d.) for patients with eGFR 15–45 ml/min/1.73 m², and 500 mg with a longer dosing interval was suggested for those with eGFR less than 15. Simulations revealed that differences in plasma AUCs between Japanese and Western patients at the same dose were mainly driven by a difference in the eGFR and that the plasma AUC after 1000 and 1500 mg b.i.d. in Japanese and Western patients, respectively, was comparable in the phase IIb studies. These results indicate suitable dosages of imeglimin in the clinical setting of T2DM with renal impairment.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Imeglimin is a first‐in‐class oral agent for the treatment of type 2 diabetes (T2DM) and is excreted unchanged into urine. A Japanese phase IIb study found that 1000 mg b.i.d. was optimal in Japanese population, and phase III studies confirmed significant glucose lowering effect. A Western phase IIb study found an optimal dose of 1500 mg b.i.d.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study addressed the key determinants of imeglimin pharmacokinetics (PKs), recommended doses for patients with renal impairment, and what drives the different optimal doses between Japanese and Western patients with T2DM.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Renal function significantly impacts imeglimin PKs. Recommended doses for patients with renal impairment have been proposed for exposure matching. Differences in estimated glomerular filtration rate (eGFR) comprised the key driver for different optimal doses at which estimated exposures were similar between Japanese and Western patients.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Doses of imeglimin could be reduced based on eGFR. Exposure responses seemed similar between Japanese and Western patients.